Opioid Therapy–Associated Cardiovascular Effects

Mary Ann E. Zagaria, PharmD, MS, BCGPClinical Consultant Pharmacist and President of MZ Associates, Inc.Hallowell, Mainewww.mzassociatesinc.comPast Chair, Board of Commissioners, Commission for Certification in Geriatric PharmacyRecipient of the Excellence in GeriatricPharmacy Practice Award from the Commission for Certification in Geriatric Pharmacy

US Pharm. 2019;44(2):9-12.

In caring for the older adult patient, it is especially difficult to evaluate and control pain in light of the multitude of pharmacologic, physiologic and psychologic aspects of care.1 There must be an ongoing focus on both the efficacy and adverse effects of opioids—the mainstay of pain treatment in all age groups—when they are prescribed to older adults with impaired metabolism, excretion, and physical reserve.1 Of particular importance in this regard is that the elderly are at greater risk for opioid-related adverse effects owing to their comorbidities and high incidence of polypharmacy.1 Among patients taking prescribed opioids, an increased cardiovascular-event rate has recently been reported in older adults.2 The opportunity for pharmacists to raise awareness of the cardiovascular adverse effects of opioids will be addressed below.

While the population of older adults in the United States continues to increase as a result of the baby-boomer generation, the concern about opioid misuse among these individuals is also increasing as it relates to overall public health.3 Even though the proportion of older adults who misuse opioids is relatively small compared with young adults, data from the National Survey on Drug Use and Health indicate that opioid misuse increased among older adults from 2013 (1.7%) to 2014 (2.0%).4 It has been estimated that the number of older adults who misuse opioids will double between 2004 and 2020, from 1.2% to 2.4%.3 Furthermore, a new report from the Agency for Healthcare Research and Quality (AHRQ) on the use of hospitals for opioid-related adverse events and opioid-use disorder among older adults indicates that5:

Between 2010 and 2015, hospitalizations related to opioid-related events increased more than 50%, and opioid-related emergency department (ED) visits more than doubled

In 2015, complications resulting from opioid use were responsible for 124,300 hospitalizations and 36,200 ED visits

Recent reports specific to the older adult population indicate inpatient hospital costs and ED charges related to opioid use increased; those admitted with a problem related to opioid use were found more likely to be discharged to another institution for postacute care versus those situations not involving opioids.5 Among other findings, the frequent use of opioids was more likely among seniors who were5:

• Poor or low income compared with those who were middle or high income

• Insured with Medicare and other public insurance compared with those who had Medicare only or Medicare and private insurance

• Living in rural areas compared with those living in urban areas.

In the noninstitutionalized population, measuring prescription-opioid use among seniors revealed that nearly one in five older adults, on average, filled at least one prescription for an opioid in 2015 and 2016; filling four or more opioid prescriptions—considered to be “frequent use”—was reported among 7% of seniors.5

The Center for Behavioral Health Statistics and Quality (CBHSQ) in the Substance Abuse and Mental Health Services Administration provides these substance-use facts from the CBHSQ Report, indicating that in adults aged 65 years and older6:

• In 2011, on an average day, there were 118 drug-related ED visits involving prescription or nonprescription pain relievers, 80 of which involved narcotic pain relievers (e.g., hydrocodone, oxycodone)

• In 2012, there was an average of six reported treatment admissions each day for heroin or other opiates.

Safe Opioid Prescribing While Avoiding Discrimination

Responsible opioid-prescribing practices encompass weighing the risks and benefits of opioid use in older adults since these agents, when appropriately prescribed, can treat pain, including debilitating pain, and (1) improve quality of life; (2) maintain independence (a key predictor of health); (3) enable mobilization; and (4) prevent homebound status.5 In an effort to curb opioid prescribing on the national level, older patients may in fact face discrimination for essentially using prescribed opioids that are necessary for quality of life; healthcare providers should be afforded education on prescribing opioids safely without discrimination.7 Patients and caregivers should be given adequate and appropriate information regarding the risks and benefits of therapy, compatible with their healthcare literacy, to understand that long-term use of opioids may be needed for palliative care or to relieve symptoms for incurable illnesses. It is recommended that avoiding polypharmacy and avoiding the use of multiple opioid agents be considered; titration to an effective dose of one opioid—as monotherapy—is preferred, when appropriate, versus small doses of multiple agents.1

Implications Related to Polypharmacy

It is likely that the effect of chronic opioids on the cardiovascular system is multifactorial.8 Notably, one reason for the recent increase in cardiovascular-related event rate with prescribed opioids in older adults might be the occurrence of nocturnal apnea and hypoxia, secondary to sleep-disordered breathing.2

As noted above, older adults are at greater risk for opioid-related adverse effects secondary to their comorbidities and high incidence of polypharmacy.1 According to the AHRQ’s 2015 data, 96% of those hospitalized for opioid-related issues had multiple chronic conditions.5 Patients aged 65 years and older have a higher burden of both underlying cardiac disease and concomitant medications that may, in combination with opioids, lead to adverse effects.8

In light of the frequent use of multiple medications for cardiovascular conditions in older adults, and the risk of cardiovascular effects of opioids in patients without cardiovascular disease, Table 1 can elucidate some of the potential medication-related cardiovascular complications associated with the opioid crisis affecting today’s seniors.

In individuals infected with HIV and concomitantly treated with methadone, QT prolongation and torsades de pointes were found to occur.9 Methadone dose correlated positively with the QTc interval prolongation; this finding underscores the risk that methadone can potentially contribute to the development of arrhythmias.9,10

Furthermore, cardiac problems in the elderly surgical patient may potentially be affected by opioid use, as symptoms of myocardial infarction in the postoperative period may be masked by analgesia or anesthesia, making diagnosis difficult.11 Opioid-use disorder has the potential to contribute to this complication. In one study of alcohol and opioid-use disorder in older adults, the authors recommend that psychiatrists increase their knowledge base regarding substance use disorders in the older adult population and provide intervention or referral for further assessment in those individuals at risk.12 For a discussion on opioid withdrawal–induced cardiomyopathy and how alcohol contributes to cardiovascular disease, see Reference 13.

Role of the Pharmacist

In order to assist in solving substance-abuse problems through prevention and treatment services, the federal Substance Abuse Prevention and Treatment Block Grant and other discretionary grant funds were developed to be administered at the state and local level.3 These were created to help the individual states in beginning to deal with substance-abuse problems by creating strategic partnerships with key stakeholders while supporting the implementation of prevention initiatives. Pharmacists can provide comprehensive recommendations, appropriate monitoring, and educational opportunities for healthcare providers (e.g., continuing education, staff development; see Reference 14 for resource) to address the nuances of opioid prescribing for older adults and substance-use disorder in the geriatric patient that underscores important issues of polypharmacy and deprescribing. Patient education would include risk-benefit discussions, informed consent concerns, and adherence guidance. These initiatives and resources may help to prevent opioid abuse and opioid therapy-related problems.